A panel of outstanding investigators surveys and explains the major cutting-edge methods used in thryroid receptor (TR) research and explains their practical experimental details. Described in step-by-step detail to ensure robust experimental results, the techniques presented cover a wide variety of key areas, including TR in development and knockout (mouse and Xenopus), transcriptional regulation by TRs in both cell-free systems and in living cells, and TR mutant analysis of patients. Additional methods provide powerful tools for the isolation of TR-regulated protein complexes, for studying the oncogene v-Erba in blood cell differentiation, and for target gene analysis in the brain. Microarray chip methods are also presented for analyzing the organs of transgenic mice to identify target genes in the liver.

The subject of this book is neuroendocrinology, that branch of biological science devoted to the interactions between the two major integrative organ systems of animals-the endocrine and nervous systems. Although this science today reflects a fusion of endocrinology and neurobiology, this synthetic ap proach is relatively recent. At the beginning of the 20th century, when the British physiologists, Bayliss and Starling, first proposed endocrinology to be an independent field of inquiry, they went to great lengths to establish the autonomy of chemical secretions in general and their independence from nervous control in particular (Bayliss, W. M. , and Starling, E. H. , 1902, The mechanism of pancreatic secretion,]. Physiol. 28:325). They argued with Pav lov, who said that there was a strong influence of the nervous system on the gastrointestinal phenomena the endocrinologists were studying. For several decades, the English physiologists prevailed, at least in the West; and Pavlov's critique was not taken to heart by the practitioners of the newly emerging discipline of endocrinology. Through the work of Harris, the Scharrers, Sawyer, Everett, and others, there has been something of a scientific detente in the latter half of this century; the hybrid field of neuroendocrinology is now regarded as one of the corner stones of modern neural science and is of fundamental importance in basic and clinical endocrinology.

Key Features: 1. Builds on its strength of having excellent content on long-term management of hyperglycemia by including pancreas and islet transplantation. 2. Contains invaluable information on glucose monitoring for healthcare professionals interested in diabetes.

I consider it an honor to have been asked to write the Foreword for The Diabetic Pancreas. Although I have been involved in the study of the pancreas since 1921, my interest goes back even further to the time, in 1918, that my father's sister, a nurse who had trained at the Massachusetts General Hospit.al, devel oped diabetes, lost weight, and died in diabetic coma. This sad event made a deep impression on me and was certainly pardy responsible for my choosing to join the Department of Physiology of the University of Toronto to begin a career in research into diabetes. This is not the place to describe in detail the wide-ranging research and study of the diabetic pancreas in which I have engaged in the past 56 years. Suffice it to say that I am familiar enough with the subject area to be able to predict a great future for this book. The editors have undertaken a very ambitious and worthwhile project, and their efforts have been supported and strengthened by contributors who are respected authorities in their fields, thus ensuring a successful presentation of this major work."

Fundamental to survival of living organisms is their ability to react appropri ately to their environment. Cannon (1929) recognized that "back of internal homeostatic mechanisms are powerful motivating agencies-appetites and hunger and thirst." Almost all observed behavior may be viewed as activity required to meet some physical or emotional need. "The higher in the scale of living things, the more numerous, the more perfect, and the more compli cated do these regulatory agencies become." This statement by Fredricq (1885) regarding internal mechanisms is at least as valid for behavior. Adrenal medullary secretion in preparation of "fight or flight" may be con sidered the first described behavioral neuroendocrine response. The conse quences of more prolonged stress on pituitary-adrenal cortical function and the subsequent unfolding of the means by which the brain controls the secre tion of the anterior and posterior pituitary glands led to the birth of neuroen docrinology. During the last decade, neuroendocrinology has taken a remarkable turn. Peptides which were believed at first to be involved solely in control of the pituitary by the hypothalamus were found in other areas of the brain. Other peptides were encountered in brain by their activity in competing for the high affinity binding of drugs to their receptors, and still others, first found in peripheral organs, were discovered also in brain. Perhaps even more amaz ing was the discovery that one or another of these peptides influence almost every aspect of behavior."

Diabetes, particularly type 2, has become increasingly more common around the world. Consequently, the effect of diabetes on the brain has achieved enormous public health importance. A surge in pre-clinical and clinical research on topics ranging from management of hyperglycemia in acute stroke to disturbances in insulin signaling in Alzheimer s disease has led to substantial progress in the field. Written by a panel of international experts, Diabetes and the Brain provides in depth reviews on the cerebral complications of diabetes, and offers introductory chapters on current insights on the pathophysiology and clinical management of diabetes, as well as neuropsychological assessment and dementia. This relevant and easily accessible book explains the cerebral complications of diabetes, with an update on diabetes for neurologists, psychiatrists, and mental health providers and researchers in general, and on stroke and dementia for those involved in research and clinical practice in diabetes."

to the Endothelin System David M. Pollock ascular endothelial cells form a monolayer lining in all of the blood vessels of V the circulation. Initially, they were thought to function as a crude filter allow- ing nutrients from the blood stream to diffuse through to the underlying tissues without letting proteins or blood cells escape. We now know that endothelial cells are important regulators of circulatory function, due in large measure to their rec- ognized ability to synthesize and release many factors that regulate vascular smooth muscle tone. Endothelial-derived factors, including relaxing and contracting sub- stances such as prostacyclin, nitric oxide (NO), and endothelin (ET), have been identified as important contributors in the regulation of vascular tone. Endothe- lial cells have a highly active metabolic function and are involved in clearing a number of agents from circulating blood. In addition, they have the enzyme that inactivates bradykinin and converts angiotensin I into the very potent pressor agent, angiotensin II (Ang II). Endothelial cells also generate various proteins like von Willebrand's factor, tissue plasminogen activator, growth promoting factors and lipids such as platelet activating factor. It is now clear that in addition to the regu- lation of vascular tone and hemodynamics, endothelial cells playa critical role in regulating growth and proliferative processes, inflammation and hemostasis.

The "Handbook on Parathyroid Diseases" presents a comprehensive and concise overview of our current knowledge in the area of parathyroid function, hormone regulation and disease states.

The Handbook educates the reader using a case-based approach presenting current evidence in the field. The material is presented in an easy to read and understandable language and uses a plethora of tables and text boxes where possible. Complex concepts are conveyed in simple and clear language. Leading international experts contribute to this state of the art book providing a true depth of knowledge and practicality.

Endocrine conditions requiring surgical intervention in the pediatric age group are uncommon. When diagnosed, they are the source of great in terest and, often, considerable debate. This is understandable, since few centers and even fewer individual surgeons can draw on vast experience of this subject. The great divergence of opinion regarding management is also understandable in that pediatric endocrine lesions often differ considerably from their adult counterparts in histology, natural history and response to treatment. Pediatric endocrine lesions are also, as a rule, less frequently malignant. In addition to the great strides made in surgical and anesthetic technique and operative monitoring, progress in four areas has substantially advanced the management of endocrine dis orders in the pediatric age group in the last decade: imaging, pathology, pharmacology and genetics. The new imaging tools, ultrasonography, computed tomography and magnetic resonance imaging, have added great diagnostic possibilities. More recent developments, such as radio nuclide imaging for the adrenal gland and the possibility of using tagged antibodies, promise to expand our imaging horizons even further. In the field of pathology, the develop ment of immunocytochemical markers (e. g. , monoclonal antibodies), the refinement in special stains and the continuous perfection of fine needle aspiration biopsies offer great new diagnostic as well as research capabil ities. Newer pharmacological agents, such as the alpha and beta blockers, the calcium channel blockers and thyroxine analogs, add a whole new level of safety to the management of the potentially lethal pheochromocytoma.

Gastroparesis is an increasingly recognized disorder. Treatment can be difficult due to the several mechanisms for symptom production. Gastroparesis: Pathophysiology, Presentation and Treatment serves as a concise reference on this disorder that allows clinicians to quickly access and evaluate the necessary information for treating and managing patients with gastroparesis. Each chapter is written byexperts in their respective area. The volume will enable the reader to better understand all aspects of this disorder. The book presents current concepts in a variety of areas opening with the epidemiology, clinical presentation and pathophysiology of gastroparesis. The natural history of patients is explored as well as evaluation of patients with suspected gastroparesis. This section includes chapters on Wireless Capsule Motility, Electrogastrography and Antroduodenal Manometry. This important resource concludes with a full section on treatment including dietary, prokinetic, antiemetic, sensory, electric stimulation, and surgical methods. New developments include the use of gastric electric stimulation for treatment, the use of SmartPill for diagnosis, and a number of new agents in development for this disorder. Gastroparesis: Pathophysiology, Presentation and Treatment is the ideal reference for gastroenterologists, and also for surgeons, endocrinologists, primary care physicians and nutritionists looking to keep pace with the latest information treatment options for their patients. "

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

Table 1 (Continuation) Reference Subject J. DAVIS, 1957, 1960b, 1961b, 1962b, 1963a; Regulation of secretion FARRELL, 1958; BARTTER et aI. , 1959; DENTON et aI. , 1959, 1960; COGHLAN et aI. , 1960; FOURMAN, 1962; MULRow and GANONG, 1962, 1964; WRIGHT, 1962; BLAIR-WEST et al. , 1963b; HOUDAS and FAVAREL- GARRIGUES, 1963 Relation of secretion to changes BARTTER, 1958 in intravascular volume Angiotensin (see Renin-angiotensin system) Blood volume and tonicity Regulation BLACK, 1954; E. BROWN et aI. , 1957; WELT, 1957; BARTTER, 1963; GAUER and HENRY, 1963 Receptors regulating SMITH, 1957 Oerebral cortex and cardiovascular function HOFF et aI. , 1963 Drugs affecting endocrine function GAUNT et al. , 1961 Erythropoietin JACOBSON, 1963; JACOBSON and DOYLE, 1963 Growth hormone (including action on adrenal cortex) FrnKEL, 1962 Hypertension Clinical and physiological aspects PAGE, 1962 SKELTON, 1959 During adrenal regeneration Renal (see Renin-angiotensin system) Russian work on SIMONSON and BROZEK, 1959 Juxtaglomerular cells Anatomy and physiology TOBIAN, 1960a, b, 1962, 1964; HATT et aI. , 1962; P. HARTROFT, 1963 Pineal and related organs KELLY, 1962 Comparative anatomy Renin-angiotensin system Chemistry, physiology, and structure- BRAUN-MENENDEZ et aI. , 1946; activity relationships BRAUN-MENENDEZ, 1956; BUMl'uS et aI. , 1961; SKEGGS, 1960; SKEGGS et aI. , 1957, 1964; PEART, 1959; GROSS and TURRIAN, 1960; PAGE and BUMl'us, 1961, 1962 Relation to hypertension in man WAKERLIN, 1955; GROSS, 1958, 1960, 1964; and animals Proceedings, Conference on Hypertension, 1958; KORNEL, 1959; TAQUINI and TAQUINI, 1961; GROSS et aI.

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It wa& decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

Paget's disease is an old disease historically, but a new disease therapeutic ally. Human remains unearthed in Lancashire, England, dating from ap proximately 900 AD, show clear evidence of the aftliction. However, it was not until the 1800s that physicians rediscovered the condition, and a little more than 100 years ago that Sir James Paget published a perceptive and accurate description of the disease from the clinical and pathologic points of view. He felt the disease represented an inflammatory condition of the skeleton and hence named it osteitis deformans. The condition again lapsed into anonymity for several decades afterwards, and therapeutic approaches did not evolve until after World War II when several groups, located mainly in the Boston area, began using a variety of agents, includ ing corticosteroids for treatment of this condition. These early attempts at therapy were unsuccessful and the condition remained essentially untreat able until the development of the calcitonins and the bisphosphonates in the 1970s. In 1978, the Paget's Disease Foundation, a private nonprofit volun tary health agency, was founded to assist individuals aftlicted by Paget's disease of bone, to provide education regarding this condition to the medical community, and to encourage research efforts to better under stand and treat the condition. An international conference was organized under the aegis of the Paget's Disease Foundation and was held in New York City in October, 1989, ten years after the founding of the Paget's Disease Foundation."

A panel of expert clinical and basic investigators summarize the state-of-the-art in the use of transgenic technology in a broad range of endocrinological applications. Up-to-date and comprehensive, Transgenics in Endocrinology reviews the most recent developments in the analysis of endocrine physiology and its pathologies through mouse models, and provides a host of creative approaches to understand better the complex processes that are characteristic of hormonal systems.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

Diagnostic Methods in Clinical Thyroidology provides a forum for discussion of controversial issues in three major categories: diagnosis of thyroid function, non-invasive evaluation of structural abnormalities, and needle biopsy diagnosis of thyroid nodules. For each category, a free interchange of ideas based on extensive clinical experience is followed by a summary that strives to resolve these controversial issues within a framework of sound clinical practice. The volume will this serve as a ready reference for the many physicians who evaluate thyroid patients.

The cytochemical bioassay system was described in a short abstract in 1971, and more fully, in the cytochemical bioassay of corticotrophin, in 1972. Since then, cytochemical bioassays have been described for several polypeptide hormones, and these assays are already widely used. It is expedient that the subject should be reviewed, as it is in this monograph, by one writer who has had the good fortune to have taken part in the growth of cytochemistry from its early origins to its present position as the basis of possibly the most sensitive bioassay system currently available. However, it should be noted that major contributions have been made by many, both to the development of the subject and to the establishment of the bioassays. The object of this preface is to try to give some perspective to the growth of this subject and to record that the cytochemical bioassay system has been fostered by many outstanding scientists in an atmosphere of remarkable goodwill. To begin with, there could have been no cytochemical bioassays until cytochem istry had been converted from its rather unsure origins into a precise and quantitative form of cellular biochemistry. This was done with skill and enthusiastic dedication by my colleagues, Dr. Lucille Bitensky, Dr. F. P. Altman, Dr. R. G. L. W. Poulter and Mr. A. A. Silcox, first at the Royal College of Butcher, Dr."

From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.

Acromegaly is a relatively rare chronic disease. Nevertheless, it is life-threatening in its sequelae, for example, hypertension and cardiovascular disease. Since it also has disfiguring properties - especially of the head and face - acromegaly has serious psychological consequences which are reinforced by the awareness of factors such as excessive sweating. It is precisely on these signs and symptoms that Sandostatin R has a rapid effect, thus improving the patient's quality of life as well as counteracting the underlying processes. SandostatinE

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.